Baseline resistance-guided therapy does not enhance the response to interferon-free treatment of HCV infection in real life

Abstract

Hepatitis C virus (HCV) response to direct-acting antivirals (DAAs) may be influenced by the presence of resistance-associated substitutions (RASs). This study aimed to assess if NS5A baseline RAS-guided treatment enhances the rate of sustained viral response (SVR) in naïve HCV-infected patients in clinical practice. All HCV-infected patients who initiated treatment with interferon (IFN)-free DAA-based regimens between March 2016 and May 2017 in 17 Spanish hospitals and who had evaluable SVR 12 weeks (SVR12) after the end of therapy were included. Patients had to be DAA naïve, with the exception of sofosbuvir with/without IFN. In one hospital, participants received therapy guided by the presence of NS5A-RASs (RGT population). Patients enrolled in the remaining hospitals, without baseline RASs testing, constituted the control population. A total of 120 and 512 patients were included in the RGT and control populations, respectively. Nine (7.5%) individuals in the RGT population showed baseline NS5A-RASs. All of them achieved SVR12. The SVR12 rate in the RGT population was 97.2% (three relapses) whereas it was 98.8% (six relapses) in the control population (p = 0.382). Our findings suggest that testing for baseline NS5A-RASs in naïve HCV-infected patients does not enhance the rate of SVR to DAA-based IFN-free therapy in clinical practice.

Treatment outcomes in hepatitis C virus genotype 1a infected patients with and without baseline NS5A resistance‐associated substitutions

“…Although we included patients with <800 000 IU/mL (for whom RAS testing is not recommended), SVR rates were comparable to previous data from clinical and real‐world studies 6,7,13,14,23 . All other regimens with an 8‐ to 12‐week duration were also highly effective with SVR rates of ≥97%, which agrees with other reports 3,26‐29 . In patients with baseline NS5A RASs who were treated according to the guidelines, the overall SVR rate was still 95%.…”

“…6,7,13,14,23 All other regimens with an 8-to 12-week duration were also highly effective with SVR rates of ≥97%, which agrees with other reports. 3,[26][27][28][29] In patients with baseline NS5A RASs who were treated according to the guidelines, the overall SVR rate was still 95%. Overall, the SVR rates for the individual regimens in patients with and without baseline NS5A RASs varied only slightly and the differences were not statistically significant.…”

Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

“…The presence of naturally‐occurring baseline RASs in NS5B and mostly in NS5A has been assessed in several studies and also can influence treatment outcome . However, current studies have suggested that routine testing of baseline RASs in naïve HCV‐infected patients does not improve the SVR rate or have a minimal (1%‐3%) effect on patient responses . For this reason, recommendations for testing baseline RAS are contradictory.…”